Dosage control electrode for iontophoresis device

ABSTRACT

An electrode assembly for use in an iontophoresis device for the transcutaneous administration of an active therapeutic species has a base layer of including a linking conductive base material which is consumed (oxidizes or reduces) preferentially to water, a first upper layer of sacrificial material coated on a first portion of the base layer wherein the sacrificial material is consumed preferentially to the linking conductive base material of the base layer. A second upper layer of non-conducting material is coated on a second portion of the base layer, the second upper layer being spaced from the first upper layer, connected by a narrow exposed linking area of the base layer material remaining exposed therebetween. During operation of an associated iontophoresis device, the sacrificial material will be sequentially consumed; the first upper layer will be fully consumed followed by the linking conductive base material of the exposed linking area of the base layer which severs the base layer thereby breaking circuit continuity disabling activity in the device. A visual indicator may be provided allowing a wearer to monitor the state of reaction of the linking area.

This application is a continuation-in-part of U.S. patent applicationSer. No. 10/371,532, filed Feb. 21, 2003. That application is deemedincorporated herein by reference in its entirety for any purpose.

BACKGROUND OF THE INVENTION

I. Field of the Invention

The present invention relates generally to iontophoresis devices for thetransdermal delivery of active agents by the use of an appliedelectromotive force (emf). More particularly, the present invention isdirected to an electrode assembly for an associated iontophoresis devicewhich incorporates an accurate, positive circuit breaking element thatstops electrical activity in the iontophoresis device after theadministration of a given total quantity of active agent.

II. Related Art

It is known to construct an iontophoresis device designed to administera given is total quantity of active agent based on the consumption of aconsumable electrode leading to a break in electrical conductivity inthe iontophoresis circuit. As used throughout this specification, theterms “consumable”, “consumed”, or the like, refer to materials that areoxidized or reduced in the operation of the corresponding iontophoresisdevice. Such arrangements are illustrated and described, for example, inU.S. Pat. No. 5,320,731 in which an iontophoresis device is constructedhaving a signal generator connected to a pair of electrodes, one ofwhich is a limiting consumable electrode, i.e., one containing a limitedquantity of material preferentially electrochemically consumed (oxidizedor reduced) in relation to the other materials of the iontophoresisdevice. The quantity of electricity necessary for complete reaction ofthe material designed to be electrochemically consumed is also designedto correspond to the quantity necessary to deliver the desired amount ofactive material to be administered by the iontophoresis device.

The consumable electrode material is applied in the form of a coating onan insulating surface or, alternatively, on a conducting support whichis unreactive, i.e., does not oxidize or reduce in the environment ofthe device. When the consumable material has been reacted, the materialbecomes non-conducting and so the current path between the pair ofelectrodes is severed and delivery by iontophoresis stops.

While devices heretofore developed using the principle of incorporatinga consumable electrode to limit agent delivery by iontophoresis havebeen based on sound theory, most have had certain drawbacks which havelimited their useful application. Examples of such prior art consumableelectrode configurations are represented in rudimentary schematic formin FIGS. 1(a)-1(c) which are side elevational or sectional viewsdepicting the layered structure of prior art consumable electrode modelsof the circuit breaking type. These models are described as consumable(oxidizable) anode assemblies or partial electrophoresis systems for thedelivery of a therapeutic agent but, of course, the concepts illustratedapply equally to consumption by reduction in cathode systems.

In FIG. 1(a), an anode assembly is shown generally at 10 and includespartial top layer 12 which represents the active ingredient-containingpad, a sacrificial metal-containing electrode layer 14 and a base layer16 which selectively may be a non-electrically conducting (insulating)material or an electrically conductive material that is not consumed inthe system. The theoretical concept is that when the consumable anodematerial located beneath the active ingredient pad 12 is fully consumed,a break will occur in the electrical circuit of the device. This isillustrated in FIG. 1(b) where the portion 18 of the consumablemetal-containing layer 14 is indicated as having been consumed therebybreaking circuit continuity at 20. This, of course, represents the idealsituation in which the portion 18 is entirely consumed prior to thebreaking or failing of the circuit.

It is well known, however, that layers of material, and particularlythin layers of material, under such circumstances are generally consumedat random which allows consumption in a manner which may well isolate aportion of the layer from the rest thereby precluding total consumptionof the consumable material, and thereby also causing premature failureof the electrode. This situation is illustrated in FIG. 1(c) wherein acentral portion of the layer 14 is shown consumed at 22 and, although aplan view is not shown, this consumed central portion is deemed toextend all the way across the layer thereby isolating distal portion 24of the sacrificial material prior to full consumption as at 18 in FIG.1(b).

The situation illustrated in FIG. 1(c) can be avoided by making the baselayer 16 electrically conductive but inert with respect to beingoxidized or reduced. This will allow all the desired sacrificialmaterial to be consumed as at 18 in FIG. 1(b); however, even after thistakes place, the circuit remains intact as conduction is maintainedalong the electrically conductive base layer. This has a potentiallyserious drawback in that any water in the system may thereafter beoxidized or reduced producing corresponding pH changes in the system atthe surface of the layer 16. Such pH changes in the system are quiteundesirable because they can cause adverse reactions with the skin of apatient to which the iontophoresis device has been applied andprevention of just such changes in pH has been a long-sought goal in theoperation of such devices. Additionally, if the drug is dissolved in awater solution (as is typical) there is an abundance of water presentand an additional amount, possibly an overdosage of drug will bedelivered in accordance with the amount of water electrochemicallyconsumed by oxidation or reduction.

Of course, if the base material 16 is not only conductive, but is amaterial that will be oxidized or reduced in the device, then thismaterial too will be consumed in an unpredictable fashion again infusingan uncertainty as to the amount of active material that will actually bedelivered by the device.

Accordingly, there is a need to provide more accurate control of thecircuit breaking characteristic associated with sacrificial orconsumable electrode materials in iontophoresis devices.

SUMMARY OF THE INVENTION

By means of the present invention, there is provided an electrodeassembly for use in an associated iontophoresis device for thetranscutaneous administration of an active therapeutic species whichincorporates an accurate and positive shutoff or circuit breaking devicein the electrode or associated circuit structure. The electrode assemblyof the present invention overcomes many of the problems and drawbacksassociated with achieving full consumption of electroactive electrodespecies to be consumed and, at the same time, provides a separate wearbar or linking element, the function of which is a positive and rapidsevering of the circuit after full consumption of the electroactiveelectrode species.

The present invention includes an electrode assembly for aniontophoresis device utilized in the transcutaneous administration of anactive therapeutic species which involves a layered structure designedto be incorporated in a conventional iontophoresis circuit. The layeredstructure includes a base layer of conductive material which reacts(oxidizes or reduces) preferentially to the oxidation or reduction ofwater. Portions or sections of the base layer are coated with two upperlayers which cover different portions of the base layer with a narrowstrip of uncoated base layer remaining therebetween. The first upperlayer contains the sacrificial or consumable material of the consumableelectrode and is coated on the first portion or area of the base layer.The consumable material of the first upper layer is selected to be onewhich oxidizes or reduces in preference to the conductive material ofthe base layer so that during the operation of the circuit of theiontophoresis device, this material is consumed first. Part of the baselayer is also covered by a second upper layer of non-conductive orinsulating material coated on a second portion of the base layer, thesecond upper layer being spaced from the first upper layer to expose anarrow gap or linking area of exposed base layer material therebetween.

It is an important aspect of the invention that when electrical currentflows through the circuit of an iontophoresis device incorporating theelectrode assembly of the invention, consumption of the consumablematerials will take place in a predetermined ordered sequence. The firstor consumable upper layer of consumable or sacrificial material will beconsumed first followed by the exposed narrow linking area of the baselayer between the consumable material of the upper layer and thenon-conducting or insulating material coated on the second portion ofthe base layer. Consumption of the much smaller narrow exposed linkingarea of the base layer serves to sever the base layer thereby breakingelectrical circuit continuity in the base layer creating an open circuitcondition thereby disabling the operation of the correspondingiontophoresis device. By design, the portion of the conductive baselayer underneath the consumable upper layer is not exposed and notconsumed, and serves to provide sound continuous electrical contact tothe upper layer during consumption of the consumable species of thatlayer.

An optional non-electrically conductive substrate layer may be utilizedbeneath the base layer, if desired. In addition, a conductive butnon-reactive layer of material may also be placed between the base layerand the first or consumable upper layer. In any event, a conductivelayer exists beneath the entire area covered by the upper layer ofsacrificially consumable material assuring that it will be consumed inits entirety. In addition, the materials of construction are selected sothat the first upper layer of sacrificial or consumable material willalso react in preference to the material of the base layer so that thefirst upper layer of sacrificial or consumable material will be entirelyconsumed prior to the consumption of any of the exposed base layer.

Preferably, the amount of consumable material in the upper layer ofconsumable or sacrificial material amounts to a larger quantity thanthat exposed in the narrow exposed linking area of the base layer. Ittypically is designed to be consumed when a designated dosage of activeagent has been administered by the corresponding iontophoresis system.The narrow exposed linking area of the base layer is preferably verynarrow and thin and, therefore, quickly consumed. In this manner, thegreat bulk of the consumable material is contained in the electrodecoating itself while the narrow exposed linking area, which might bedescribed as a “wear bar”, serves more particularly as a circuitbreaking device to turn the system off after electrode consumption. Ofcourse, the portions of the conductive base layer flanking the linkingarea or wear bar need not be of the same composition as the linking areaor even each other as these areas serve only to conduct electrons andare not exposed to solutions to be reacted.

The conductive base layer including the linking area is preferably of amaterial which indicates a visually observable change between itsoriginal appearance in an unused device and its consumed (oxidized orreduced) or open circuit state. In this regard, a skin worniontophoresis patch incorporating the electrode assembly of the presentinvention may preferably be provided with an opening or window in theupper or outer layer facing away from the skin of the user therebyexposing the linking area or wear bar to the user or other externalobserver so that the state of the exposed linking area may be observed.In this manner, the linking area can be monitored and consumption of thelinking area and with it the end of the operation of the iontophoreticpatch can be readily observed and the patch timely removed.

It should further be noted that the electrode assembly of the inventioncould be either an anode assembly in which the consumable materials areoxidized and are used up in order of their appearance in theelectromotive series or cathode electrode in which the consumablematerials are reduced preferentially to each other in the same manner.They, of course, must be electrically conducting in the unreacted stateand non-conducting in the reacted state in accordance with theinvention. Thus, consumable electrodes of the cathode type are normallychosen from salts which are conductive in oxidized form andnon-conductive in reduced form. Conversely, the consumable anodematerials are normally chosen from metals which are readily consumed byelectrochemical oxidation, for example, Al, Cu, Mg, Zn and Ag. The mostpreferred anode materials include Zn in the consumable upper layer ofsacrificial material and Ag in the base layer, also forming the narrowexposed linking area of the base layer. These materials can be usedalone or mixed with non-reactive constituents so long as the matrixremains conductive. Such binder materials are well known in the art.

The use of a conductive non-reactive layer between the base layer andthe first upper layer of consumable or sacrificial material furtherensures that the entire amount of consumable or sacrificial materialwill be reacted prior to the reaction of the underlying base layer andmaintains the circuit breaking effect of the narrow exposed linkingarea. Of course, the non-reactive conductive layer like the base layerwill be disconnected by the consumption of the narrow exposed linkingarea. Examples of these materials include platinum, titanium, stainlesssteel, gold, carbon, graphite and conducting polymers.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, wherein like numerals designate like parts throughoutthe same:

FIG. 1(a) depicts in a simplified schematic form an embodiment of aprior art anode that uses a sacrificial middle layer to limit capacity;

FIG. 1(b) depicts the designed ideal failure mode for the consumableanode of FIG. 1(a);

FIG. 1(c) depicts a probable failure mode for the anode of FIG. 1(a);

FIG. 2(a) is also a simplified schematic representation in sideelevation of one embodiment of a drug delivery anode electrode portionof an iontophoresis device fabricated in accordance with the presentinvention;

FIG. 2(b) is a greatly reduced plan view of the electrode assembly ofFIG. 2(a) showing, the relative sizes of the sacrificial metal layer andthe exposed linking area of the base layer;

FIG. 2(c) depicts the first stage of consumption of the sacrificialmetal layer of the embodiment of FIG. 2(a);

FIG. 2(d) depicts the second stage of consumption of the narrow exposedlinking area severing the continuity of the circuit;

FIGS. 3(a)-3(c) are views similar to FIGS. 2(a), 2(c) and 2(d) of analternate embodiment of the electrode assembly of the invention;

FIG. 4 represents a current-time profile for the delivery of fentanylfor patients using, the system of Example I;

FIG. 5 depicts plasma fentanyl concentrations for the two-hour periodduring and immediately post-iontophoresis; and

FIGS. 6(a) and 6(b) depict top views of an iontophoresis patch deviceincorporating an electrode assembly in accordance with the presentinvention along with a visual indicator for observation of circuitcontinuity exposing the linking area of the circuit in thepre-application or operating state and consumed or open circuit state,respectively.

DETAILED DESCRIPTION

The detailed description contains examples of possible configurations ofthe electrode assembly of the invention and these are meant by way ofexample only and not intended to be limiting in any manner as variationswill occur to those skilled in the art.

In FIGS. 2(a) and 2(b), an anode assembly is shown generally at 30 andincludes a first upper layer containing consumable or sacrificial metalmaterial at 32 which represents the initially consumed portion of theelectrode assembly of the invention. The second upper layer ofnon-conductive material is shown at 34, there remaining a narrow gap orlinking area or element 36 between the upper layers 32 and 34. Thelayers 32 and 34 are coated on a further base layer 38 and between themcovering the entire area of the base layer 38 with the exception of thenarrow or exposed linking area 36. A further optional non-electricallyconductive substrate layer of a material such as Mylar (duPont) isdepicted by the reference character 40. The layer 40 is preferablytransparent or contains an opening to thereby expose the linking elementor area 36 to an observer such as a user of a device, for example, askin worn iontophoresis patch of a design exemplified by FIGS. 6(a) and6(b). An overlaying portion 42 is provided which includes material forreceiving an active therapeutic agent to be dispensed utilizing theiontophoresis device associated with the electrode assembly.

As seen in FIG. 2(c), the entire partial top layer of consumable orsacrificial metal material 32 is shown in the reacted, oxidized orconsumed state. Thus, it is important to note that the entire amount ofthe consumable or sacrificial anode is reacted prior to the reaction ofany part of the conductive base layer 38. Also, in accordance with theinvention, only a small fraction of the conductive base area is consumedat all and this is only an amount sufficient to sever the continuouselectrical conduction through that layer. In FIG. 2(d), the second stageof the dual-reacting system has been completed and the exposed narrowneck or linking area 36 of the layer 38 has been consumed and renderednon-conducting thereby severing the electrical connection betweenportions 44 and 46 of the base layer 38. Of course, the portions 44 and46 of the base layer 38 may be of the same composition as the linkingelement or area 36 or they may be of a different composition so long asthey are able to function as conductors during the operation of thecircuit. Thus, areas 44 and 46 may contain a conductive material such asgold or carbon or other material with the wear element 36 beingpreferably of silver. As indicated, these areas are not exposed to anysolution in the device and are not designed to participate in anyreaction. The vast majority of layer 38 remains intact after the circuitis broken and the device ceases operation. Physical continuity only maybe maintained through the non-conductive optional substrate layer 40.

FIGS. 3(a)-3(c) depict an alternate embodiment of the electrode assemblyof the invention. This embodiment is similar to the embodiments depictedin FIGS. 2(a)-2(d) with the exception that an additional conductivelayer is interposed between the consumable electrode layer 32 and thebase layer 38. The material of the layer 50, although conductive, is onethat will not react in the iontophoresis environment and thereforeremains stable and ensures total consumption of the consumable electrodematerial in layer 32 as the area is totally connected in the circuit. Asseen in FIG. 3(c), the narrow exposed linking area 36 of the base layer38 is consumed after total consumption of the electrode area 32 and thisagain severs the continuous circuit.

FIGS. 6(a). and 6(b) depict top views of an iontophoresis patch device,generally at 60, including a translucent or opaque upper layer 62, andpeel-away applicator tabs as at 64 and 66. A second electrode which maycomplete a galvanic couple is shown by dash lines at 68 and anadditional circuit element including an auxiliary power source of atleast 0.1 volt is depicted at 70. A viewing opening in the layer 62 isdepicted at 72. The opening 72 need only be large enough to exposelittle more than the linking area or wear bar 36 in the layer 38. Ofcourse, the entire layer 62 may be of a transparent material obviatingthe need for the opening 72. Note that in FIG. 6(a) the system is in thenormal or pre-application state with the consumable sacrificial materiallayer 32 and the linking area 36 unreacted. In FIG. 6(b), thesacrificial material in area 32 has been depleted as has the material inthe linking area 36. In this regard, the area 36 is designed to becomediscolored when the active material is reached or consumed so as to bereadily observable by one looking into the window 72 in the layer 62.Thus, for example, silver darkens when in an oxidized state as in AgCl,etc. In this manner, the wearer or other observer can note immediatelythe condition of the linking area or element 36 and remove the patch assoon as the consumption of that (Ag) material is indicated, knowing thatthe prescribed dosage has been administered.

An important aspect of the present invention lies in the fact that atleast two materials in descending order of reactivity are utilized toprovide first, a consumable or sacrificial electrode and second, apositive circuit breaking link in the conductive base which provides aquick positive and automatically imposed shutoff system. The amount ofconsumable material in the consumable electrode layer 32 is large incomparison to the amount of consumable material in the linking area 36,typically in a ratio from about 20:1 to 1000:1, preferably from about50:1 to 250:1 and most preferably it is in the order of 100:1. Thus, thetransfer of active material by iontophoresis is designed to be completedduring the consumption of the electrode layer 32 and the consumption ofthe consumable material and linking area 36 is designed solely tooperate as a circuit breaker or shutoff device.

EXAMPLE I

Screen-printed Zn and AgCl were used as anode and cathode materials,respectively for an iontophoresis device. The Zn electrodes wereconstructed with a known amount of zinc to produce a fixed chargedosage. The configuration of the anode is illustrated in cross-sectionand plan views in FIGS. 2(a) and 2(b). A thick film paste, containing aknown amount of Zinc and resistive binder, was printed over a silverconductive layer. In operation, as described above, after consumption ofthe Zn during the passage of current, an exposed portion of the baseconductive layer is oxidized, severing electrical connection to theelectrode.

Reproducibility and accuracy of the electrodes were tested by preparingand measuring ten iontophoretic patches, having self-limiting anodesdesigned to last ten milli-amp minutes. 2% sodium citrate was loadedinto the anode reservoir, and 1% saline was loaded into the cathodereservoir. An integrated battery served to provide power. Current-timeprofiles were monitored via a voltage drop across a series resistance.

The ability of the wearable, electronic drug delivery system toadminister a fixed dosage of drug was measured by delivering fentanylinto four human volunteer subjects. The study was conducted, after IRBapproval, at Inveresk Clinical Research Ltd, Edinburgh Scotland. Devicesdesigned to administer a 10 mA-min dosage over an approximately 30minute time period were loaded with 0.5% Fentanyl Citrate in the drugreservoir, and 0.9% saline in the counter reservoir. As in thereproducibility evaluation, an integrated DC battery served as asupplemental power source, and current was monitored using anelectrometer measurement of a voltage drop across a series resistor.Blood samples were collected periodically and plasma was analyzed byLC-MS/MS.

The results of the reproducibility study are summarized as follows:measured capacity of the electrodes averaged 11.3 mA-min (range 10.6 to12.1, sd 0.49), and discharge time averaged 36.0 min (range 23 to 70, sd13.8). The results of the Fentanyl delivery study are depictedgraphically in FIGS. 4 and 5.

In FIG. 4, the current-time profiles for each of the four patients aredisplayed. In FIG. 5, plasma fentanyl concentrations are shown for thetwo-hour period during and immediately post-iontophoresis. The minimumeffective therapeutic concentration (MEC) of fentanyl has been reportedto be 0.63 ng/ml(Grond, S. et al., Clinical Pharmacokinetics ofTransdermal Opioids, Clin. Pharmacokint. 2000 Jan 38(1); pp 59-89). Thistherapeutic concentration was achieved in two patients by 15 minutes,and in the remaining two by 30 minutes. In all subjects, peak fentanylplasma concentration was achieved at 30 minutes, and was coincident withthe suspension of iontophoretic current.

The devices were well tolerated in all subjects, with no adverse effectsnoted outside of those expected from the drug itself.

This invention has been described herein in considerable detail in orderto comply with the patent statutes and to provide those skilled in theart with the information needed to apply the novel principles and toconstruct and use such specialized components as are required. However,it is to be understood that the invention can be carried out byspecifically different equipment and devices, and that variousmodifications, both as to the equipment and operating procedures, can beaccomplished without departing from the scope of the invention itself.

1. A relatively planer, layered electrode assembly suitable for use inan electrical circuit associated with an iontophoresis device for thetranscutaneous administration of an active therapeutic speciescomprising: (a) a base layer comprising at least in part a linkingconductive base material which is electrochemically consumedpreferentially to water oxidation or reduction; (b) a first upper layerof sacrificial electrode material coated on a first portion of said baselayer wherein said sacrificial electrode material is electrochemicallyconsumed in the same manner but preferentially to said linkingconductive base material of said base layer; (c) a second upper layer ofnon-conducting material coated on a second portion of said base layer,said second upper layer being spaced from said first upper layer, anarrow linking area of said linking conductive base material remainingexposed therebetween, wherein said linking area of said base layerextends across said base layer; and (d) wherein, as said electrodeassembly is used in a circuit of an associated iontophoresis device,during the operation thereof, consumption of said materials is orderedwith said first upper layer of sacrificial electrode material beingconsumed first and said exposed linking area including said linkingconductive base material of said base layer being consumed second,consumption of said linking conductive base material interruptingelectrical circuit continuity in said electrode assembly and disablingiontophoresis activity in said associated device.
 2. An electrodeassembly for an iontophoresis device as in claim 1 further comprising anon-electrically conductive substrate layer beneath said base layer. 3.An electrode assembly for an iontophoresis device as in claim 1 furthercomprising a conductive non-reacting layer between said base layer andsaid first upper layer.
 4. An electrode assembly for an iontophoresisdevice as in claim 2 further comprising a conductive non-reacting layerbetween said base layer and said first upper layer.
 5. An electrodeassembly for an iontophoresis device as in claim 1 wherein saidsacrificial material of said first upper layer and said conductivematerial of said exposed linking area of said base layer are supplied ina total amount essentially corresponding to that necessary to transporta designed predetermined dosage amount of active therapeutic material tobe transcutaneously administered by said iontophoresis device.
 6. Anelectrode assembly as in claim 1 wherein the ratio of the amount of saidsacrificial electrode material to the amount of said linking area ofconducting base material is from about 20:1 to 1000:1.
 7. An electrodeassembly as in claim 6 wherein said ratio is about 100:1.
 8. Anelectrode assembly as in claim 1 wherein said electrode assembly iscontained in a skin worn iontophoresis device, said device furthercomprising a visual indicator for observing the state of reaction ofsaid linking area.
 9. An electrode assembly as in claim 8 wherein saidvisual indicator includes observable discoloration of said conductingbase material when an active species is consumed.
 10. An electrodeassembly as in claim 8 wherein said iontophoresis device includes anopaque upper layer and wherein said visual indicator is accessed throughan opening in said opaque upper layer.
 11. An electrode assembly as inclaim 9 wherein said iontophoresis device includes an opaque upper layerand wherein said visual indicator is accessed through an opening in saidopaque upper layer.
 12. An electrode assembly as in claim 8 wherein saidiontophoresis device includes a transparent upper layer that exposes thevisual indicator.
 13. An electrode assembly as in claim 9 wherein saidiontophoresis device includes a transparent upper layer that exposes thevisual indicator.
 14. An electrode assembly as in claim 1 wherein saidbase layer is of a homogenous composition.
 15. An electrode assembly asin claim 1 wherein said base layer includes a plurality of conductivematerials.
 16. An electrode assembly as in claim 1 wherein consumptionis by oxidation.
 17. An electrode assembly as in claim 1 wherein saidexposed linking area includes silver.
 18. An electrode assembly as inclaim 9 wherein said active species of said visual indicator includessilver.
 19. An electrode assembly as in claim 15 wherein said base layerincludes a material selected from the group consisting of gold andcarbon.
 20. A relatively planer, layered electrode assembly suitable foran associated iontophoresis device operable in the transcutaneousadministration of an active therapeutic species comprising: (a) a baselayer including an amount of a linking conductive base material whichoxidizes preferentially to water oxidation; (b) a first upper layer ofsacrificial electrode material coated on a first portion of said baselayer wherein said sacrificial electrode material oxidizespreferentially to said conductive base material of said base layer; (c)a second upper layer of non-conducting material coated on a secondportion of said base layer, said second upper layer being spaced fromsaid first upper layer, a narrow linking area including said linkingconductive base material remaining exposed therebetween, wherein saidlinking area of said base layer extends across said base layer; and (d)wherein, as said electrode assembly is used in a circuit of anassociated iontophoresis device, consumption of materials is orderedsuch that said first upper layer of sacrificial electrode material isconsumed first, and said linking conductive base material is consumedsecond consumption of said linking conductive base material severingsaid base layer; interrupting electrical circuit continuity in saidelectrode assembly and disabling iontophoresis activity in an associateddevice.
 21. An electrode assembly for an iontophoresis device as inclaim 20 wherein said sacrificial material of said first upper layerincludes zinc and wherein said base layer linking conductive basematerial comprises silver.
 22. An electrode assembly for aniontophoresis device as in claim 20 further comprising anon-electrically conductive substrate layer beneath said base layer. 23.An electrode assembly for an iontophoresis device as in claim 20 furthercomprising a conductive non-oxidizing layer between said base layer andsaid first upper layer.
 24. An electrode assembly for an iontophoresisdevice as in claim 22 further comprising a conductive non-oxidizinglayer between said base layer and said first upper layer.
 25. Anelectrode assembly as in claim 20 wherein said electrode assembly iscontained in a skin worn iontophoresis device, said device furthercomprising a visual indicator for observing the state of reaction ofsaid linking area.
 26. An electrode assembly as in claim 25 wherein saidiontophoresis device includes an opaque upper layer and wherein saidvisual indicator comprises an opening in said opaque upper layer.
 27. Amethod of operating an iontophoresis circuit wherein the amount ofactive agent transferred by iontophoresis is governed by the consumptionof a consumable electrode, the method including the step of providing aseparate consumable circuit breaking device which is consumed in orderedsequence after said consumable electrode material and which reacts inpreference to water.
 28. A method as in claim 27 comprising the furthersteps of incorporating said iontophoresis circuit in a skin worniontophoresis patch device and providing visual access in a surface ofsaid patch device such that the state of said consumable circuitbreaking device can be observed when the patch is in place.
 29. A skinworn iontophoresis device including the electrode assembly of claim 1.